Dendritic HCN2 Channels Constrain Glutamate-Driven Excitability in Reticular Thalamic Neurons
| Autor: | Peter A. Goldstein, Fan Jia, Shui-Wang Ying, Franz Hofmann, Andreas Ludwig, Syed Y. Abbas |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Potassium Channels
Dendritic spine Glutamic Acid AMPA receptor Ion Channels Mice Thalamus Postsynaptic potential Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels HCN channel Animals gamma-Aminobutyric Acid Mice Knockout Neurons biology Reticular Formation General Neuroscience Glutamate receptor Excitatory Postsynaptic Potentials Dendrites Articles Hyperpolarization (biology) Receptors Glutamate nervous system biology.protein Excitatory postsynaptic potential GABAergic Neuroscience |
| Zdroj: | The Journal of Neuroscience. 27:8719-8732 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1630-07.2007 |
| Popis: | Hyperpolarization activated cyclic nucleotide (HCN) gated channels conduct a current,Ih; howIhinfluences excitability and spike firing depends primarily on channel distribution in subcellular compartments. For example, dendritic expression of HCN1 normalizes somatic voltage responses and spike output in hippocampal and cortical neurons. We reported previously that HCN2 is predominantly expressed in dendritic spines in reticular thalamic nucleus (RTN) neurons, but the functional impact of such nonsomatic HCN2 expression remains unknown. We examined the role of HCN2 expression in regulating RTN excitability and GABAergic output from RTN to thalamocortical relay neurons using wild-type and HCN2 knock-out mice. Pharmacological blockade ofIhsignificantly increased spike firing in RTN neurons and large spontaneous IPSC frequency in relay neurons; conversely, pharmacological enhancement of HCN channel function decreased spontaneous IPSC frequency. HCN2 deletion abolishedIhin RTN neurons and significantly decreased sensitivity to 8-bromo-cAMP and lamotrigine. Recapitulating the effects ofIhblock, HCN2 deletion increased both temporal summation of EPSPs in RTN neurons as well as GABAergic output to postsynaptic relay neurons. The enhanced excitability of RTN neurons afterIhblock required activation of ionotropic glutamate receptors; consistent with this was the colocalization of HCN2 and glutamate receptor 4 subunit immunoreactivities in dendritic spines of RTN neurons. The results indicate that, in mouse RTN neurons, HCN2 is the primary functional isoform underlyingIhand expression of HCN2 constrains excitatory synaptic integration. |
| Databáze: | OpenAIRE |
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